Mean platelet volume as a predictor of cardiovascular risk: a systematic review and meta-analysis

See also Machin SJ, Briggs C. Mean platelet volume: a quick, easy determinant of thrombotic risk? This issue, pp 146–7. Summary. Aim:   To determine whether an association exists between mean platelet volume (MPV) and acute myocardial infarction (AMI) and other cardiovascular events. Platelet activity is a major culprit in atherothrombotic events. MPV, which is widely available in clinical practice, is a potentially useful biomarker of platelet activity in the setting of cardiovascular disease. Methods and Results:   We performed a systematic review and meta‐analysis investigating the association between MPV and AMI, all‐cause mortality following myocardial infarction, and restenosis following coronary angioplasty. Results were pooled using random‐effects modeling. Pooled results from 16 cross‐sectional studies involving 2809 patients investigating the association of MPV and AMI indicated that MPV was significantly higher in those with AMI than those without AMI [mean difference 0.92 fL, 95% confidence interval (CI) 0.67–1.16, P < 0.001). In subgroup analyses, significant differences in MPV existed between subjects with AMI, subjects with stable coronary disease (P < 0.001), and stable controls (P < 0.001), but not vs. those with unstable angina (P = 0.24). Pooled results from three cohort studies involving 3184 patients evaluating the risk of death following AMI demonstrated that an elevated MPV increased the odds of death as compared with a normal MPV (11.5% vs. 7.1%, odds ratio 1.65, 95% CI 1.12–2.52, P = 0.012). Pooled results from five cohort studies involving 430 patients who underwent coronary angioplasty revealed that MPV was significantly higher in patients who developed restenosis than in those who did not develop restenosis (mean difference 0.98 fL, 95% CI 0.74–1.21, P < 0.001). Conclusions:   Elevated MPV is associated with AMI, mortality following myocardial infarction, and restenosis following coronary angioplasty. These data suggest that MPV is a potentially useful prognostic biomarker in patients with cardiovascular disease. Whether the relationship is causal, and whether MPV should influence practice or guide therapy, remains unknown.     

Is mild normobaric hypoxia a risk factor for venous thromboembolism?

Summary.  Background : Modern air travel entails a cabin altitude between 1520 and 2440 m (5000–8000 ft) and thus exposure to mild hypoxia. There is debate as to whether hypoxia is causally related to venous thromboembolism (VTE) occurring during or after travel. One study suggested that a short period of hypobaric hypoxia causes activation of coagulation. Objectives : To test the hypothesis that hypoxia alone (normobaric hypoxia) causes activation of coagulation, possibly through endothelial cell activation. Methods : Six healthy male volunteers were exposed for 3 h, while seated, on two separate occasions to (i) dry air (control) and (ii) hypoxic gas mixture (12.8% O₂ in N₂, equivalent to breathing air at 3660 m [12000 ft]). Results : There were no differences in hemostatic or endothelial markers between control and hypoxic groups, but platelet and leukocyte counts increased and were significantly higher in the hypoxic group. There were increases in fibrinogen and von Willebrand factor, as well as rheological changes, but these were not significantly different between control and hypoxic groups. Conclusions : This small study does not support the previous suggestion that hypoxia causes activation of coagulation, and suggests that immobility-induced rheological changes may be more significant in the etiology of VTE occurring during or after travel.     

Coffee consumption and the risk of venous thromboembolism: the Tromsø study

Summary. Background: Several studies have investigated the association between coffee consumption and cardiovascular disease, but little is known about coffee intake and the risk of venous thromboembolism (VTE). Objective: The aim of this prospective cohort study was to investigate the association between coffee consumption and the risk of incident VTE in a general population. Methods: Information about coffee consumption habits was obtained with a self‐administered questionnaire in 26 755 subjects, aged 25–97 years, who participated in the fourth survey of the Tromsø study (1994–1995). Incident VTE events were registered until the end of follow‐up, 1 September 2007. Results: There were 462 incident VTE events (1.60 per 1000 person‐years, 95% confidence interval [CI] 1.46–1.75) during a median of 12.5 years of follow‐up. A daily consumption of three to four cups was borderline associated (hazard ratio [HR] 0.70; 95% CI 0.48–1.02) and a daily consumption of five to six cups (HR 0.67; 95% CI 0.45–0.97) was significantly associated with reduced risk of VTE as compared with coffee abstainers in multivariable analysis adjusted for age, sex, body mass index (BMI), smoking status, physical activity, diabetes, history of cardiovascular disease and cancer. Similar risk estimates were found for provoked and unprovoked VTE, and in sex‐stratified analyses. Conclusion: Our findings suggest a possible U‐shaped relationship between coffee consumption and VTE, and that moderate coffee consumption may be associated with a reduced risk of VTE. However, more studies are needed to establish whether moderate coffee consumption is inversely associated with the risk of VTE.     

Familial risk of venous thromboembolism: a nationwide cohort study

Background: Venous thromboembolism has genetic determinants, but population‐based data on familial risks are limited. Objectives: To examine the familial risk of venous thromboembolism. Methods: We undertook a nationwide study of a cohort of patients with deep venous thrombosis or pulmonary embolism born after 1952. We used the Danish National Registry of Patients covering all Danish hospitals, for the years 1977 through 2009, to identify index cases of venous thromboembolism, and assessed the incidence among their siblings. We compared standardized incidence ratios (SIRs) of the observed and expected number of venous thromboembolism cases among siblings, using population‐specific, gender‐specific and age‐specific incidence rates. Results: We identified 30 179 siblings of 19 599 cases of venous thromboembolism. The incidence among siblings was 2.2 cases per 1000 person‐years, representing a relative risk of 3.08 (95% confidence interval [CI] 2.80–3.39) as compared with the general population. The risk was higher for both men (SIR 3.36, 95% CI 2.96–3.82) and women (SIR 2.81, 95% CI 2.45–3.23). The risk was similar among siblings of index cases with venous thrombosis and those of index cases with pulmonary embolism. Conclusion: Venous thromboembolism has a strong familial component.     

Mean platelet volume is increased in patients with severe obstructive sleep apnea

Abstract

Increased platelet activation and aggregation which are closely related to cardiovascular complications have been reported in patients with obstructive sleep apnea (OSA). The aim of this study was to assess the mean platelet volume (MPV), an indicator of platelet activation in patients with OSA. The 95 subjects referred for evaluation of OSA underwent overnight polysomnography. Blood samples were taken for MPV determination. According to the apnea-hypopnea index (AHI), subjects were divided into three groups; group 1: control subjects without OSA (AHI < 5, n = 24), group 2: patients with mild to moderate OSA (AHI: 5–30, n = 42), and group 3: severe OSA (AHI > 30, n = 29). Body mass index (BMI) of patients with severe OSA was significantly higher than control subjects (31.5 ± 4.0 vs. 28.2 ± 5.0; p = 0.02). The MPV was significantly higher in patients with severe OSA than in the control group (8.9 ± 1.0 vs. 8.2 ± 0.7 fl; p = 0.01). Correlation analysis within 71 patients with OSA indicated that MPV was correlated with AHI (p < 0.001, r = 0.44) and DI (p = 0.001, r = 0.37). In multivariate regression analysis, when MPV was taken as independent with other study variables which are potential confounders such as age, gender and BMI, MPV was independently correlated with both AHI (β = 0.44, p < 0.001) and DI (β = 0.38, p < 0.001). We have shown that MPV was significantly higher in patients with severe OSA when compared with control subjects and MPV was correlated with AHI and DI.     

Thrombomodulin gene polymorphisms or haplotypes as potential risk factors for venous thromboembolism: a population-based case–control study

Dysfunction of the protein C anticoagulant system is associated with venous thromboembolism (VTE) and thrombomodulin (TM) is a critical cofactor within the protein C system. The aim of this study was to test the hypotheses that polymorphisms or haplotypes within the TM gene are common risk factors for VTE. We screened the TM putative promoter, exon and 3'-untranslated region for sequence variations in a random sample (n = 266) of consecutive idiopathic, objectively confirmed non-Olmsted County VTE patients referred to the Mayo Clinic. We then genotyped a sample of Olmsted County, MN residents with a first lifetime, objectively confirmed VTE in the 25-year period, 1966-90 (n = 223), and a sample of Olmsted County residents without VTE (n = 237) for polymorphisms either discovered in the screening population or previously published, and tested for an association of VTE with TM genotype or haplotypes using unconditional logistic regression and generalized linear models, respectively. We also genotyped these Olmsted County cases and controls at 20 'null' genetic maker loci and tested for population admixture. Nine novel and three previously described mutations were identified in the screening population. Mutations within the TM promoter, EGF(1-5), serine/threonine-rich, transmembrane, and cytoplasm regions were absent or uncommon. TM845G-->A (Ala25Thr; lectin region), TM2136T-->C (Ala455Val; EGF(6) region), TM2470C deletion (3'-untranslated region), and 4363A-->G (3'-flanking region) were more common, but were not associated with VTE by genotype or haplotype. Null genetic marker allele frequencies did not differ significantly among cases and controls. We conclude that polymorphisms or haplotypes within the TM gene are not common risk factors for incident VTE.     

Poor anticoagulation quality in the first 3 months after unprovoked venous thromboembolism is a risk factor for long-term recurrence

BACKGROUND AND AIM: Several factors are associated with an increased risk of recurrent venous thromboembolism (VTE). The aim of the study was to investigate whether the quality of oral anticoagulation therapy (OAT) is a long-term risk factor for recurrence of VTE after OAT interruption. METHODS AND RESULTS: A total of 297 patients (170 males) with a recent acute unprovoked VTE episode were prospectively monitored during OAT in our anticoagulation clinic and followed up for 21 months after OAT interruption. Recurrent events were recorded in 42 subjects for 493 years of follow-up [14.1% of patients; 8.5% patient-years (pt-y)] after OAT withdrawal. The rate of recurrence was not correlated to OAT duration. Subjects experiencing recurrence after OAT interruption had spent significantly more time at markedly subtherapeutic international normalized ratio (INR) levels (<1.5) and less time within the therapeutic range (2.0-3.0 INR) during OAT. Relative risk (RR) of recurrence was significantly higher [2.77 (95% confidence interval (CI) 1.49-5.18; P = 0.001) and 2.70 (95% CI 1.39-5.25; P = 0.003) at univariate and multivariate analysis, respectively] in those who spent more time (upper quintile) at INR values <1.5, being especially evident in the first 90 days of OAT. RR was significantly higher at univariate [2.05 (95% CI 1.07-3.96; P = 0.031)] but not at multivariate [1.98 (95% CI 0.98-4.0; P = 0.056)] analysis when the entire OAT period was considered. Subjects in the upper quintile of time spent at INR values <1.5 had significantly higher D-dimer values when OAT was stopped and after 3 months. CONCLUSIONS: The amount of time that subjects with an acute unprovoked VTE event spend at near-normal INR values (<1.5) during the first 3 months of treatment is associated with higher D-dimer values measured during OAT and after its interruption and is a significant risk factor for late VTE recurrence.     

Mean platelet volume and the ratio of mean platelet volume to platelet count in the diagnosis of acute appendicitis

Background

Mean platelet volume (MPV) is an inflammatory marker. Recent studies have shown that there is a negative correlation between platelet count (PC) and MPV and that the ratio of these two values may be more meaningful. The aim of our study was to investigate the diagnostic value of MPV and the MPV/PC ratio in acute appendicitis.

Mean platelet volume/platelet count ratio predicts severe pneumonia of COVID‐19

BackgroundAlthough platelet mean volume/platelet count ratio (MPR) is considered to be a crucial marker of inflammatory and infectious diseases, the relationship between MPR and novel coronavirus infectious disease 2019 (COVID‐19) remains unclear.MethodsIn this retrospective study, 85 patients with confirmed COVID‐19 were enrolled and divided into low and high MPR group. Data from repeated measures were compared by the generalized estimating equations. Cox regression analyses were performed to assess the impact of MPR on the incidence of severe pneumonia (SP), with inverse probability of treatment weighting (IPTW) used to reduce confounding bias. The primary outcome is the incidence of SP of COVID‐19.ResultsDuring follow‐up, 17 (20.0%) patients were developed to SP. Compared with mild patients, patients with SP developed showed a higher MPR level at baseline, day 1, day 2, and day 3 after admission (P = .005, P = .015, P = .009, and P = .032, respectively). Kaplan‐Meier method showed a higher incidence of SP in the high MPR group than the low MPR group (log‐rank test = 10.66, P = .001). After adjustment, high MPR was associated with an elevated incidence of SP (HR, 5.841, 95% CI, 1.566‐21.791, P = .009). The IPTW method also suggested that MPR was a significant factor related to the incidence of SP (HR, 8.337, 95% CI, 4.045‐17.182, P < .001).ConclusionHigh MPR level is an independent risk factor for severe pneumonia in patients with COVID‐19.     

Insulin resistance and risk of venous thromboembolism: results of a population‐based cohort study

Summary. Background: Obesity is an established risk factor for venous thromboembolism (VTE), but it is uncertain how this is mediated. Insulin resistance has a central role in the pathophysiology of the metabolic effects of obesity. Objective: We aimed to investigate whether insulin resistance is a risk factor for VTE. Methods: For this analysis we used the PREVEND prospective community‐based observational cohort study. Insulin resistance was measured as HOMA‐IR (homeostasis model assessment of insulin resistance) and fasting insulin. VTE was assessed using databases of the national registries of hospital discharge diagnoses, death certificates and the regional anticoagulation clinic. Results: Out of 7393 subjects, 114 developed VTE during a median follow‐up of 10.5 years. High HOMA‐IR was associated with increased risk of VTE after adjustment for traditional cardiovascular risk factors, CRP and markers of endothelial dysfunction (hazard ratio [HR], 1.38; 95% confidence interval [95% CI], 1.09–1.75; P = 0.007). When body mass index (BMI) was added to the model, BMI was a strong risk predictor for VTE (HR, 1.53; 95% CI, 1.24–1.88; P < 0.001) whereas HOMA‐IR no longer showed such an association (HR, 1.11; 95% CI, 0.85–1.43; P = 0.45). Results were similar for fasting insulin. Conclusion: Our population‐based cohort study shows an increased risk of VTE in subjects with increasing insulin resistance but not independently of BMI.     

The first ambulatory screening on thromboembolism: a multicentre, cross-sectional, observational study on risk factors for venous thromboembolism

Summary.  Objectives:  To assess the prevalence of risk factors for venous thromboembolism (VTE) and the prevalence of recent (<1 year) VTE [including superficial vein thrombosis (SVT), deep vein thrombosis (DVT) and pulmonary embolism (PE)] amongst patients attending general practitioner (GP) surgeries. Design:  Multicentre, cross-sectional, observational study. Setting:  A total of 1536 GP surgeries. Participants:  A total of 15 180 adult, co-operative subjects, who had consulted their GP for a health disorder and signed the informed consent form. Interventions:  None. Main outcome measures:  Prevalence of known VTE risk factors graded according to importance and prevalence of recent (<1 year) VTE events (including SVT), based on interviews. Results:  About 1:5 patients had at least one strong risk factor and about 1:20 had at least two risk factors, with no difference between sexes. The prevalence of strong risk factors increased with age. Most were related to medical conditions: history of SVT and/or DVT/PE, heart failure and malignancy. About 3:4 women and 2:3 men had at least one moderate to weak risk factor; nearly 1:2 women and 1:3 men had at least two moderate to weak risk factors. The most common were: history of VTE, smoking, history of miscarriage, estrogen therapy, obesity, and varicose veins. Overall, 80% women and 67% men had at least one risk factor, and 50% women and 35% men had at least two risk factors. The prevalence of recent (<1 year) VTE was 3.4% in women and 2.4% in men, and increased with age. The majority of cases were SVT in both sexes (2.5% in women and 1.5% in men). Conclusions:  The prevalence of risk factors for VTE amongst patients attending GP surgeries is high. GPs should bear this in mind during their daily practice.     

High platelet count associated with venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS)

Summary.  Background:  In cancer patients, laboratory parameters that predict venous thromboembolism (VTE) are scarce. Increased platelet count has been found to be a risk factor for VTE in cancer patients receiving chemotherapy (CHT). We have assessed high platelet count as a risk predictor for VTE in patients with cancer undergoing discriminative anti-cancer treatments and investigated whether platelet count correlates with thrombopoietin (TPO) levels. Design and methods:  The Cancer and Thrombosis Study (CATS) is an ongoing prospective observational study of patients with newly diagnosed cancer or progression of disease, which started in October 2003. Occurrence of VTE and information on the patients' anti-cancer treatment during follow-up were recorded. Results: Between October 2003 and February 2008, 665 patients with solid tumors were included (314 female/351 male, mean age 62 years). VTE occurred in 44 patients (18 female/26 male, mean age 62 years). The cumulative probability of VTE after 1 year was 34.3% in patients with a platelet count (PC) above the 95th percentile representing 443 × 10⁹/L compared with 5.9% in those below 443 × 10⁹/L. High platelet count [hazard ratio (HR): 3.50, 95% confidence interval (CI): 1.52–8.06, P  = 0.0032], soluble P-selectin [HR: 2.66, 95% CI: 1.42–4.96, P  = 0.0021] and surgery [HR: 4.05, 95% CI: 1.74–9.46, P  = 0.0012] were statistically significant risk factors for VTE in multivariable analysis along with leucocyte count, age, gender, radio- and CHT. We found no correlation between platelet count and TPO levels. Conclusions:  High PC is a clinically important, independent risk predictor for VTE in cancer patients. PC was not found to be associated with TPO levels.     

Family history of myocardial infarction is an independent risk factor for venous thromboembolism: the Tromsø study

Summary. Background: Recent studies indicate that arterial cardiovascular diseases and venous thromboembolism (VTE) share common risk factors. A family history of myocardial infarction (MI) is a strong and independent risk factor for future MI. Objectives: The purpose of the present study was to determine the impact of cardiovascular risk factors, including family history of MI, on the incidence of VTE in a prospective, population‐based study. Patients and methods: Traditional cardiovascular risk factors and family history of MI were registered in 21 330 subjects, aged 25–96 years, enrolled in the Tromsø study in 1994–95. First‐lifetime VTE events during follow‐up were registered up to 1 September 2007. Results: There were 327 VTE events (1.40 per 1000 person‐years), 138 (42%) unprovoked, during a mean of 10.9 years of follow‐up. In age‐ and gender‐adjusted analysis, age [hazard ratio (HR) per decade, 1.97; 95% confidence interval (CI), 1.82–2.12], gender (men vs. women; HR, 1.25; 95% CI, 1.01–1.55), body mass index (BMI; HR per 3 kg m^?2, 1.21; 95% CI, 1.13–1.31), and family history of MI (HR, 1.31; 95% CI, 1.04–1.65) were significantly associated with VTE. Family history of MI remained a significant risk factor for total VTE (HR, 1.27; 95% CI, 1.01–1.60) and unprovoked VTE (HR, 1.46; 95% CI, 1.03–2.07) in multivariable analysis. Blood pressure, total cholesterol, HDL‐cholesterol, triglycerides, and smoking were not independently associated with total VTE. Conclusions: Family history of MI is a risk factor for both MI and VTE, and provides further evidence of a link between venous and arterial thrombosis.